Correlation of tumor characteristics derived from DCE-MRI and DW-MRI with histology in murine models of breast cancer

The purpose of this work was to determine the relationship between the apparent diffusion coefficient (ADC, from diffusion-weighted (DW) MRI), the extravascular, extracellular volume fraction (v(e), from dynamic contrast-enhanced (DCE) MRI), and histological measurement of the extracellular space fraction. Athymic nude mice were injected with either human epidermal growth factor receptor 2 positive (HER2+) BT474 (n = 15) or triple negative MDA-MB-231 (n = 20) breast cancer cells, treated with either Herceptin (n = 8), Abraxane (low dose n = 7, high dose n = 6), or saline (n = 7 for each cell line), and imaged using DW- and DCE-MRI before, during, and after treatment. After the final imaging acquisition, the tissue was resected and evaluated by histological analysis. H & E-stained central slices were scanned using a digital brightfield microscope and evaluated with thresholding techniques to calculate the extracellular space. For both BT474 and MDA-MB-231, the median ADC of the central slice exhibited a significantly positive correlation with the corresponding central slice extracellular space as measured by H & E (p = 0.03, p < 0.01, respectively). Median v(e) calculated from the central slice showed differing results between the two cell lines. For BT474, a significant correlation between v(e) and extracellular space was calculated (p = 0.02), while MDA-MB-231 tumors did not demonstrate a significant correlation (p = 0.64). Additionally, there was no correlation discovered between ADC and v(e) with either whole tumor analysis or central slice analysis (p > 0.05). While ADC correlates well with the histologically determined fraction of extracellular space, these data add to the growing body of literature that suggests that v(e) derived from DCE-MRI is not a reliable biomarker of extracellular space for a range of physiological conditions. Copyright (C) 2015 John Wiley & Sons, Ltd.